This research is to study the structure and function of three glycoproteins showing a close correlation with malignancy, i.e., fibronectin and two major membrane glycoproteins with Mr = 90 to 100 and 150 kilodaltons. Fibronectin is the major pericellular glycoprotein mediating cell-cell or cell-substratum adhesion, promoting cytokinesis, and influencing the expression of various cellular phenotypes. Loss of this glycoprotein, together with other matrix glycoproteins associated with oncogenic transformation, has been observed in many, if not all, transformed cells. Four distinctive functional domains have been isolated and characterized from hamster plasma-form fibronectin, and the carbohydrate structure of cellular and plasma forms have been elucidated. We will continue to study: (1)\functional domains and structures of cellular-form, released-form, and tumor cells; (2)\amino acid sequences of the functional domains; (3)\the dissection of the 150 kilodalton fragment into possible subdomains capable of binding heparin, causing cell adhesion, and for cytokinesis; (4)\mechanisms of fibronectin changes associated with transformation, cell contact, and cell cycle; (5)\carbohydrate structure in human fibronectins, cellular-form, released-form, and transformed cells; and (6)\functional alternation by fibronectin. Although preliminary data suggest that carbohydrate composition of the 90 to 110 and 150 kilodalton glycoproteins are closely related to the degree of tumorigenicity and malignancy of the cells, the exact changes of their structures as related to tumorigenicity are unknown. The change of their carbohydrate structures as related to their functional changes of proteins and to their dependency on cell proliferation will be explored. The 150 kilodalton glycoprotein (Koyama et al.; see Progress Report) will be studied, focusing on its carbohydrate structure and possible ability in promoting Ca2+-dependent cell-cell adhesion. The degree of sialyation of this molecule may define the cell adhesive property of this protein and the degree of malignancy of cells. (A)